MPC-19 DIAGNOSTIC APPROACH IN HISTOPATHOLOGICALLY CHALLENGING CASES IN KYOTO UNIVERSITY HOSPITAL

In 2021, the WHO classification of tumors of the central nervous system (CNS) was published, which drastically changed the diagnostic approach to tumors in the CNS. In the diagnosis of most subtypes of CNS tumors, especially in gliomas, the genetic test became critical in the latest version of the classification, meanwhile analyzing genetic alterations in routine practice is still quite difficult in most of the hospitals in Japan because of the accessibility of the genetic analysis. In Kyoto University Hospital (KUHP), around 80 tumors in CNS are newly diagnosed every year, half of which are gliomas with a few challenging cases on the histopathological diagnosis. The diagnostic approach to CNS tumors in KUHP can be divided into two steps: the clinical phase and the academic phase. The clinical phase includes a pre-operative conference with neurosurgeons, radiologists, and pathologists, and classical histopathological analysis on formalin-fixed and paraffin-embedded tissues with H&E staining, immunohistochemistry on p53, IDH1 R132H, and ATRX, fluorescence in situ hybridization on 1p/19q co-deletion, and consultation to the experts of the CNS tumors. Some cases are further analyzed by clinical cancer genome sequencing. When the tumors are expected to be glioma during the pre-operative conference, after the surgery, the tumor tissue gets frozen to be submitted to the academic phase. The academic phase includes analysis of genetic alterations with Sanger sequencing and Multiplex Ligation-dependent Probe Amplification (MLPA) assay on the representative glioma-associated genes. In some cases, the tumors are further analyzed by methylome assay and/or mRNA sequencing (PMID: 35900258), to identify novel genetic alterations. Most of the neuropathologists in Japan today are suffering in diagnosing gliomas because of the novel, sophisticated, and complicated WHO classification. In this presentation, we want to share our diagnostic approach to the diagnosis of CNS tumors and shed light on it.